The aim of these studies is to determine whether drugs which block the transport of nucleosides and nucleobases across the cell membrane can modulate the selectivity of methotrexate (MTX) and other antimetabolites. Experiments will seek to determine whether nitrobenzyltioinosine and dipyridamole are capable of modulating the toxicity of MTX by virtue of their ability to interfere with the transport of thymidine and hypoxanthine. These studies will be carried out both in vitro using human tumor cells, and in vivo with the L1210 murine leukemia model. Additional studies will be directed at assessing the ability of dipyridamole to a) increase the selectivity of cytosine arabinoside (ara-C) in the L1210 model, and b) to interfere with the regulation of the de novo purine and pyrimidine pathways mediated by salvage pathway metabolites. Pharmacologic studies of dipyridamole will be performed to determine whether systemic administration of dipyridamole concurrently with intracavitary administration of ara-C can increase the therapeutic ratio of ara-C against tumor confined to the pleural or peritoneal cavities.